There are over 15 million diagnosed cases of diabetes in the United States alone. According to the American Diabetes Association, about 60-70% of people with diabetes have mild to severe forms of diabetes-related nerve damage. Diabetic neuropathy is a condition that encompasses a wide range of dysfunction. Neuropathic ulcers or lesions of the foot resulting from diabetic neuropathy are a major cause of lower leg amputations. In fact, progression of diabetic foot ulcers is the leading cause of non-traumatic lower limb amputations in the United States. The risk of a leg amputation is 15-40 times greater for a person with diabetes.
Loss of protective sensation and repetitive trauma (e.g. walking) are major causes of such ulcers. Loss of tone in the small muscles of the feet cause changes in the architecture of the foot that ultimately result in increased pressure over the ball of the foot. This increased pressure causes calluses and eventually ulceration.
These lesions are associated with microcirculatory compromise, resulting in the breakdown of dermal integrity. The etiology is thought to be progressive endothelial vessel injury induced by chronic hyperglycemia. While neuropathy, trauma, and infection secondarily promote foot lesion extension, the underlying pathology for these conditions and the ulcer itself is chronic hyperglycemia resulting in compromised vascular flow to the skin. Once developed, these ulcers become chronic conditions lasting indefinitely. It is not unusual for ulcers of this type to persist for many years. Unlike common trauma-induced superficial wounds, chronic diabetic ulcers penetrate deep into the patient's tissue, often exhibiting penetration completely through the dermis, leaving the ulcer open and exposing underlying structures such as tendon, muscle or bone.
Current therapy for diabetic foot ulcers is inadequate, as evidenced by the high incidence of healing failure (See Ramsey et al., Diabetes Care 22:382-387, 1999). Conventional therapies include debridement of necrotic tissue, repeated sterile dressings, use of orthotic devices to reduce pressure, bed rest, and aggressive use of antibiotics to fight infection. Conventional therapy does not address the underlying pathology of microangiopathy in the lower extremity, but seeks to provide enough covering to prevent ulcer extension and possible amputation. Cell-based coverings are sometimes used to treat ulcers, such coverings including autologous skin flaps, skin grafts, or cultured skin layers such as APLIGRAF™. However, providing a covering that may or may not assist in closure does nothing to treat the underlying pathology, which is compromised circulation in combination with compromised sensation. As such, the rate of recurrence of healed ulcers is as high as 80%. There remains a need in the art for therapeutic methods for treating chronic ulcers, such as diabetes-related ulcers.